The Population Genetics Analysis program is focused on human genetic variation underlying differential immune responses to vaccination against or infection by human pathogens. The goals are to replicate previously identified human genotype-phenotype associations and elucidate the functional relevance of the validated genetic variants that correlate with immune outcome. Research will focus on one or more of the emerging or re-emerging Group I, II, or III infectious agents listed at http://www3.niaid.nih.gov/topics/emerging/list.htm. This information will help to identify individual risk factors, will expand our understanding of immune mechanisms applicable to a broad range of human diseases, and will help define biomarkers of risk and immunity that might lead to novel diagnostic tests of infection or vaccine response. This contract will study the genetic variants associated with smallpox vaccine immune response heterogeneity